Use of highly parallel snp genotyping for fetal diagnosis

Abstract

The present invention provides apparatus and methods for enriching components or cells from a sample and conducting genetic analysis, such as SNP genotyping to provide diagnostic results for fetal disorders or conditions.

1 . A method for detecting fetal abnormality comprising: 
 a. determining a ratio of abundance of maternal allele(s) to abundance of paternal allele(s) in genomic DNA from fetal cells enriched from a maternal blood sample using size-based separation.    
     
     
         2 . The method of  claim 1 , wherein said genomic DNA comprises one or more SNPs.  
     
     
         3 . The method of  claim 2 , wherein said SNP is informative.  
     
     
         4 . (canceled)  
     
     
         5 . The method of  claim 2 , wherein said one or more SNPs are in a single locus, different loci, single chromosome, or different chromosomes.  
     
     
         6 . The method of  claim 1 , wherein said genomic DNA comprises a paternal allele that differs from both maternal alleles.  
     
     
         7 . The method of  claim 2 , wherein a first region of genomic DNA is trisomic or suspected of being trisomic and a second region of genomic DNA is non-trisomic or suspected of not being trisomic.  
     
     
         8 . The method of  claim 7 , further comprising the step of comparing said ratio of abundance of maternal allele(s) to abundance of paternal allele(s) in said first genomic DNA region with said ratio of abundance of maternal allele(s) to abundance of paternal allele(s) in said second genomic DNA region.  
     
     
         9 . The method of  claim 8 , wherein an increase in paternal abundance in said first region is indicative of paternal trisomy.  
     
     
         10 . The method of  claim 8 , wherein an increase in maternal abundance in said first region is indicative of maternal trisomy.  
     
     
         11 . The method of  claim 8 , wherein said first genomic region and said second genomic region are on the same chromosome.  
     
     
         12 . The method of  claim 11 , wherein an increase in paternal abundance or maternal abundance of one or more alleles is indicative of partial trisomy.  
     
     
         13 - 14 . (canceled)  
     
     
         15 . The method of  claim 1 , wherein said determining step comprises detecting an abundance of a nucleotide base at a SNP position.  
     
     
         16 . The method of  claim 2 , wherein said SNP is detected using a DNA microarray, bead microarray, or high throughput sequencing.  
     
     
         17 . The method of  claim 1 , further comprising enriching said sample for fetal cells prior to determining allele abundance.  
     
     
         18 . (canceled)  
     
     
         19 . A method for detecting fetal abnormality comprising: 
 b. enriching a maternal blood sample for fetal cells using size-based separation;    c. determining a ratio of allele abundance in said enriched maternal blood sample by comparing an abundance of one or more maternal alleles in a first genomic region with an abundance of one or more maternal alleles in a second genomic region,    d. wherein said first genomic region is trisomic or suspected of trisomy, and    e. wherein said second genomic region is non-trisomic.    
     
     
         20 . The method of  claim 19 , wherein said maternal alleles in a first genomic region comprise an SNP.  
     
     
         21 . The method of  claim 19 , wherein said maternal alleles in a second genomic region comprise an SNP.  
     
     
         22 . The method of  claim 19 , further comprising comparing said ratio to a second ratio obtained for a control sample.  
     
     
         23 . The method of  claim 22 , wherein said control sample comprises a diluted portion of said maternal blood sample.  
     
     
         24 - 25 . (canceled)  
     
     
         26 . The method of  claim 19 , further comprising ranking said alleles by allele abundance.  
     
     
         27 . The method of  claim 26 , further comprising using said ranked alleles to determine an abundance of one or more paternal alleles.  
     
     
         28 . The method of  claim 27 , further comprising comparing the abundance of said one or more paternal alleles to the abundance of said maternal alleles at one or more genetic regions.  
     
     
         29 - 31 . (canceled)  
     
     
         32 . The method of  claim 19 , wherein said first genomic region suspected of trisomy is selected from the group consisting of chromosomes 13, 18, 21 and X.  
     
     
         33 . The method of  claim 19 , wherein said second genomic region that is non-trisomic is selected from the group consisting of chromosomes 13, 18, 21 and X.  
     
     
         34 - 35 . (canceled)  
     
     
         36 . A method for detecting fetal abnormality comprising: 
 f. comparing an abundance of one or more maternal alleles in genomic DNA in a maternal blood sample with an abundance of one or more maternal alleles in said genomic DNA in a blood sample, wherein    g. a first region of said genomic DNA is trisomic or suspected of trisomy, and,    h. a second region of said genomic DNA is non-trisomic.    
     
     
         37 - 52 . (canceled)